There are four major areas of investigation. The first of these is an investigation of immune mechanisms operative in EAE. The specific aims include, 1) to characterize affinity-purified rat antibodies to encephalitogenic peptides 68-85 and 68-88 of GPBP, 2) to prepare anti-idiotypic antisera reactive with each characterized rat anti-peptide antibody, 3) to localize the idiotypic determinant(s) to H-chains, L-chains, or both, of the rat anti-peptide antibodies, and 4) to assess the ability of the anti-idiotypic antibodies to alter the function of T-lymphocytes involved in EAE. The second area of investigation is into the structure, metabolism and function of myelin basic protein. The specific aims of this project include 1) to sequence the small and large rat basic proteins to see if there are additional differences between them besides the 40 residue deletion, 2) determine the extent of basic protein dimers in myelin, and study its distribution in myelin density gradient fractions, 3) measure the turnover of myelin proteins in different myelin density gradient fractions, and 4) determine the structural relationships between myelin basic protein and its possible larger precursor. The specific aim of the third area is to identify an antigen within normal and/or multiple sclerosis CNS tissue which will react with MS cerebrospinal fluid IgG. The fourth area is concerned with the enzyme 2',3'-cyclic nucleotide 2'-phosphohydrolase (CNP). The specific aims are to isolate the enzyme and to localize it in CNS tissues by the technique of EM histocytochemistry. A second aim is to identify a physiological substrate of the enzyme.